期刊
JOURNAL OF PROTEOME RESEARCH
卷 14, 期 10, 页码 4394-4401出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.5b00703
关键词
N-linked glycosylation; INLIGHT; ovarian cancer; relative quantification; cancer biomarker; human plasma
资金
- National Institutes of Health National Cancer Institute Innovative Molecular Analysis Technologies (NIH NCI IMAT) Program [R33 (CA147988-02)]
- NIH National Institute of General Medical Sciences (NIGMS) Graduate Training in Molecular Biotechnology at NC State [T32GM008776]
- W.M. Keck Foundation
- North Carolina State University
An early-stage, population-wide biomarker for ovarian cancer (OVC) is essential to reverse its high mortality rate. Aberrant glycosylation by OVC has been reported, but studies have yet to identify an N-glycan with sufficiently high specificity. We curated a human biorepository of 82 case-control plasma samples, with 27%, 12%, 46%, and 15% falling across stages I-IV, respectively. For relative quantitation, glycans were analyzed by the individuality normalization when labeling with glycan hydrazide tags (INLIGHT) strategy for enhanced electrospray ionization, MS/MS analysis. Sixty-three glycan cancer burden ratios (GBRs), defined as the log(10) ratio of the case-control extracted ion chromatogram abundances, were calculated above the limit of detection. The final GBR models, built using stepwise forward regression, included three significant terms: OVC stage, normalized mean GBR, and tag chemical purity; glycan class, fucosylation, or sialylation were not significant variables. After Bonferroni correction, seven N-glycans were identified as significant (p < 0.05), and after false discovery rate correction, an additional four glycans were determined to be significant (p < 0.05), with one borderline (p = 0.05). For all N-glycans, the vectors of the effects from stages II-IV were sequentially reversed, suggesting potential biological changes in OVC morphology or in host response.
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